[No authors listed]
Systemic sclerosis (SSc) is a chronic autoimmune inflammatory disease characterized by extensive tissue fibrosis and various vascular complications. A wealth of evidence suggests the substantial contribution of pro-inflammatory cytokines to the development of SSc, but the role of interleukin (IL)-18 signaling in this disease still remains elusive. To address this issue, we herein determined serum levels of IL-18-binding protein isoform a (IL-18BPa), a soluble decoy receptor for IL-18, by enzyme-linked immunosorbent assay in 57 SSc patients and 20 healthy controls and evaluated their clinical correlation. Serum IL-18BPa levels were higher in SSc patients than in healthy controls, while comparable between diffuse cutaneous SSc and limited cutaneous SSc patients. Although serum IL-18BPa levels were not associated with dermal and pulmonary fibrotic parameters in SSc patients, there was a significant positive correlation between serum IL-18BPa levels and right ventricular systolic pressure estimated by echocardiography. Furthermore, in 24 SSc patients who underwent right heart catheterization, serum IL-18BPa levels positively correlated with mean pulmonary arterial pressure. As for systemic inflammatory markers, significant positive correlations of circulating IL-18BPa levels with erythrocyte sedimentation rate and C-reactive protein were noted. These results suggest that the inhibition of IL-18 signaling by IL-18BPa may be involved in the development of pulmonary vascular involvement leading to pulmonary hypertension and modulate the systemic inflammation in SSc.
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